This invention relates to steroids useful as diagnostic agents.
There is a need for accurate and highly sensitive analytical methods for active substances, for example, steroids, which can be present in extremely small quantities, in body fluids, e.g., blood, urine, etc. The analysis must respond, if at all possible, only to the specific active substance, a steroid. In other words, the analysis must be specific and not give false positives by the presence of other substances in the same sample of body fluid.
A plurality of analytical methods already exists which are based on a great variety of physicochemical processes, e.g., spectrometry, titrimetry, chromatography, etc. Because of the minute amounts of substances to be detected or detectable, immunological testing methods have gained increasing popularity in the determination of active substances, e.g., of steroids, since immunological testing methods, more specifically radioimmunological tests, are generally superior, due to their sensitivity and specificity, to other testing methods in the determination of active agents inherent in the body or similar active agents.
A prerequisite of a radioimmunological test is that a sufficiently specific antiserum must be available and the compound to be detected, or a suitable derivative thereof, must be available as a tracer in a maximally high radioactively marked form.
The production of a specific antiserum can be accomplished relatively easily if the antigen to be detected is itself capable of stimulating the formation of antibodies, i.e., it is also an immunogen. This holds true, inter alia, for all proteohormones which, in an extremely highly purified form, can be used directly for the production of suitable antisera. The problem becomes more complicated if the antigen is a low-molecular compound, such as a steroid, for example, which itself does not provoke an immune response, i.e., is not immunogenic.
In such cases, the linking of the low-molecular antigen, frequently also called haptene, e.g., a steroid, to a high-molecular carrier, and the use of this "conjugate" as immunogen has proven itself satisfactorily. However, a basic disadvantage of this process is that the linking of the haptene to the high-molecular carrier leads to a reduction in the specificity of the thus-obtained antibodies, as is the case in the majority of the antisera presently available. The loss in specificity manifests itself in the cross reactions of the antisera with other active substances, e.g., steroids, exhibiting characteristic functional groups similar to those of the steroid to be detected. This is due to the fact that the characteristic functional groups are employed for the linking of the haptene to the high-molecular carrier, so that the functional groups cannot take part as determinants during the stimulation of the antibody synthesis and thus cannot contribute to the specificity of the thus-formed antibodies.
Also, the above-mentioned second prerequisite, viz., the accessibility of sufficiently highly radioactively labeled tracers, is not fulfilled in many cases, especially in the case of steroids used as active substances so that in spite of the possibility of producing the desired antisera, radioimmunological determination of these steroids cannot be accomplished.
For this reason, highly radioactively labeled steroid derivatives, which are readily obtainable and can be used as tracers, would represent a substantial advance in the art of diagnostic agents.
The present invention now makes available radioactively tagged steroid derivatives which do not have the disadvantages described hereinabove.